The goal of this project is to develop a complete thermodynamic characterization of the contributions of the entropic terms involved in protein folding. This characterization implies: - Experimental determination of the enthalpy (~ H), entropy (~ S), and heat capacity (~ Cp) components of the Gibbs free energy (~ G) for different peptides in which different contributions can be dissected. - Structural thermodynamic analysis aimed at: 1) partitioning the polar and apolar contributions to the experimentally measured enthalpy and heat capacity changes; and, 2) evaluating the solvent and configurational contributions to the entropy change for the backbone, the side chain entropy and the cratic term. These studies use a combination of high sensitivity differential scanning calorimetry in order to measure the heat capacity function of several mutants of a 33 amino acid synthetic peptide corresponding to the leucine zipper (coiled-coil) region of the yeast transcription factor GCN4. Parallel control experiments are performed by CD spectroscopy and ultracentrifugation. The crystallographic structure of the coiled coil structure formed by this peptide is known at high resolution. The amino acid substitutions are located at position 14, which corresponds to a solvent exposed site away from the dimerization interface. So far, the mutants S14A, S14H, S14G A24G and S14V have been synthesized as well as some others peptides with cysteines to study the cratic term. DSC experiments for each mutant are being performed under a variety of appropriate conditions. As a result of this study, the paper ~The Magnitude of the Backbone Conformational Entropy in Protein Folding~ by J. Alejandro D~Aquino, Javier Gomez, Vincent Hilser, Kon Ho Lee, L Mario Amzel and Ernesto Freire was submitted and accepted for publication in Proteins.